Trifluoroacetic acid → HCID 58641321, compound

Participants

Reaction Steps

A solution of tert-butyl(2S)-4-(2,5-difluorophenyl)-2-methyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxylate (21-3, prepared from tert-butyl(2S,4S)-4-hydroxy-2-methyl-2-phenylpyrrolidine-1-carboxylate (21-2) by the procedures of Scheme 20, 24 mg, 0.065 mmol, 1 equiv) in a 1:1 mixture of trifluoroacetic acid and dichloromethane (10 mL) was stirred for 30 minutes, then concentrated. The residue was dried via toluene azeotrope (2×10 mL), then dissolved in dichloromethane (10 mL). Triethylamine (0.090 mL, 0.65 mmol, 10 equiv) and dimethylcarbamoyl chloride (0.030 mL, 0.33 mmol, 5.0 equiv) were added, and the resulting mixture was stirred at 40° C. for 6 hours, then 23° C. for 2 days. The reaction mixture was partitioned between aqueous saturated sodium bicarbonate solution (30 mL) and ethyl acetate (2×25 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (hexanes initially, grading to 40% ethyl acetate in hexanes) to provide (2S)-4-(2,5-difluorophenyl)-N,N,2-trimethyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide (21-4) as an off-white solid. 1H NMR (500 MD, CDCl3) δ 7.40 (br d, 2H, J=7.7 Hz), 7.32 (br t, 2H, J=7.8 Hz), 7.22 (t, 1H, J=7.5 Hz), 7.08-6.91 (m, 3H), 6.24 (m, 1H), 4.82 (dd, 1H, J=13.9, 1.5 Hz), 4.77 (dd, 1H, J=13.9, 1.5 Hz), 2.77 (s, 6H), 2.02 (s, 3H). LRMS m/z (M+H) 343.0 found, 343.2 required.

Provenance & Evidence